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Immunohistochemical quantification of the cobalamin transport protein, cell surface receptor and Ki-67 in naturally occurring canine and feline malignant tumors and in adjacent normal tissues.

Sysel AM, Valli VE, Bauer JA - Oncotarget (2015)

Bottom Line: This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues.Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species.These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors.

View Article: PubMed Central - PubMed

Affiliation: Bauer Research Foundation, Akron, Ohio, USA.

ABSTRACT
Cancer cells have an obligate need for cobalamin (vitamin B12) to enable DNA synthesis necessary for cellular replication. This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues. All malignant tumor tissues stained positively for TCII, TCII-R and Ki-67 proteins; expression varied both within and between tumor types. Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species. There was a strong correlation between TCII and TCII-R expression, and a modest correlation between TCII-R and Ki-67 expression in both species; a modest association between TCII and Ki-67 expression was present in canine tissues only. These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors. The potential to utilize these proteins as biomarkers to identify neoplastic tissues, streamline therapeutic options, evaluate response to anti-tumor therapy and monitor for recurrent disease has important implications in the advancement of cancer management for both human and companion animal patients.

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Related in: MedlinePlus

Conservation of TCII and TCII-R amino acid sequence homology between human and canine and between human and feline speciesSequences are illustrated using the 2014 Ensembl Comparative Genomics Orthologue alignments. (A) TCII amino acid sequence. (B) TCII-R amino acid sequence.
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Figure 5: Conservation of TCII and TCII-R amino acid sequence homology between human and canine and between human and feline speciesSequences are illustrated using the 2014 Ensembl Comparative Genomics Orthologue alignments. (A) TCII amino acid sequence. (B) TCII-R amino acid sequence.

Mentions: The primary TCII and TCII-R antibodies used in this study were commercially available rabbit polyclonal antibodies raised to human TCII and TCII-R antigens, and this study is the first to evaluate them in canine and feline tissues. Both TCII and TCII-R proteins are expressed in all mammals. Based on comparison of primary sequences, the amino acids involved in TCII-Cbl binding, the cysteine residues involved in disulfide bonds, the TCII-R-encoding gene structure and the TCII-R flanking DNA, all appear to be highly conserved across species [13]. We evaluated human, canine and feline protein sequence files from the Ensembl genome browser (Ensembl 2014, release 76, URL http://useast.ensembl.org/index.html) using the Ensembl Comparative Genomics Orthologue function to identify regions of similar protein alignment between the biologic sequences for the TCII and TCII-R genes (Figure 5). We identified 73% sequence similarity between human TCII and both canine/feline TCII, and 83% sequence similarity between canine and feline TCII. There was a 57% (canine) and 62% (feline) TCII-R protein sequence similarity to human, and a 76% similarity between canine and feline TCII-R sequences. The high degree of similarity between human, canine and feline TCII and TCII-R protein sequences, as well as length of similar antigen peptide regions recognized by the TCII and TCII-R primary antibodies permitted successful binding of human-specific primary antibodies in the canine and feline tissues used for IHC staining in this study.


Immunohistochemical quantification of the cobalamin transport protein, cell surface receptor and Ki-67 in naturally occurring canine and feline malignant tumors and in adjacent normal tissues.

Sysel AM, Valli VE, Bauer JA - Oncotarget (2015)

Conservation of TCII and TCII-R amino acid sequence homology between human and canine and between human and feline speciesSequences are illustrated using the 2014 Ensembl Comparative Genomics Orthologue alignments. (A) TCII amino acid sequence. (B) TCII-R amino acid sequence.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385855&req=5

Figure 5: Conservation of TCII and TCII-R amino acid sequence homology between human and canine and between human and feline speciesSequences are illustrated using the 2014 Ensembl Comparative Genomics Orthologue alignments. (A) TCII amino acid sequence. (B) TCII-R amino acid sequence.
Mentions: The primary TCII and TCII-R antibodies used in this study were commercially available rabbit polyclonal antibodies raised to human TCII and TCII-R antigens, and this study is the first to evaluate them in canine and feline tissues. Both TCII and TCII-R proteins are expressed in all mammals. Based on comparison of primary sequences, the amino acids involved in TCII-Cbl binding, the cysteine residues involved in disulfide bonds, the TCII-R-encoding gene structure and the TCII-R flanking DNA, all appear to be highly conserved across species [13]. We evaluated human, canine and feline protein sequence files from the Ensembl genome browser (Ensembl 2014, release 76, URL http://useast.ensembl.org/index.html) using the Ensembl Comparative Genomics Orthologue function to identify regions of similar protein alignment between the biologic sequences for the TCII and TCII-R genes (Figure 5). We identified 73% sequence similarity between human TCII and both canine/feline TCII, and 83% sequence similarity between canine and feline TCII. There was a 57% (canine) and 62% (feline) TCII-R protein sequence similarity to human, and a 76% similarity between canine and feline TCII-R sequences. The high degree of similarity between human, canine and feline TCII and TCII-R protein sequences, as well as length of similar antigen peptide regions recognized by the TCII and TCII-R primary antibodies permitted successful binding of human-specific primary antibodies in the canine and feline tissues used for IHC staining in this study.

Bottom Line: This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues.Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species.These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors.

View Article: PubMed Central - PubMed

Affiliation: Bauer Research Foundation, Akron, Ohio, USA.

ABSTRACT
Cancer cells have an obligate need for cobalamin (vitamin B12) to enable DNA synthesis necessary for cellular replication. This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues. All malignant tumor tissues stained positively for TCII, TCII-R and Ki-67 proteins; expression varied both within and between tumor types. Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species. There was a strong correlation between TCII and TCII-R expression, and a modest correlation between TCII-R and Ki-67 expression in both species; a modest association between TCII and Ki-67 expression was present in canine tissues only. These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors. The potential to utilize these proteins as biomarkers to identify neoplastic tissues, streamline therapeutic options, evaluate response to anti-tumor therapy and monitor for recurrent disease has important implications in the advancement of cancer management for both human and companion animal patients.

Show MeSH
Related in: MedlinePlus